Another interesting day in Kiev and with the staff at EmCell. In the morning I started the day out with more families starting their first course of stem cell therapies. This group included a breast cancer survivor with autoimmune problems and three children with autism and immune dysfunction. The youngest was 4 and she did much better than expected during the usual challenge of blood specimen collect and as usual the skilled nursing staff collected the specimen on the first try (not an easy feat for many of our children on the autism spectrum). They were successful in getting her IV infusion for round one of stem cells, but not without a major tantrum over having her arm held during the process. She was never in pain, but the emotional trauma of having someone restrain her arm was enough to trigger a major meltdown. Not that this is unusual and many of us who live with someone on the spectrum see just how easily they fall apart when the sensory environment and obsessive interests are not immediately satisfied.

The challenge for the doctors is they rightfully want to examine the non-sedated child, yet the child often is intolerant of the entire process. This faces all of use in clinical practice when we attempt our examinations and diagnostic/therapeutic interventions.

After this I spent the rest of the afternoon with Dr Karpenko learning about the rich heritage of the Ukrainian people and the City of Kiev.

Dr Karpenko escorted Aaron around a 3 hour walking tour of the city on his first day after stem cell therapy and he was remarkably calm and interested in the new surroundings.

Dominating the landscape of the city is this huge titanium monument to the victories painfully won in WWII. The statue reminds me to never, never, never give up with the battle to help children with autism.

And Kiev is not without its elegant European architecture. The orthodox churches, opera house and stylish cityscapes made for a pleasant adventure for our first post-transplantation adventure.

This is the famous Philharmonic house – reported to have the finest acoustics in the World.

And while this beautiful Orthodox cathedral appears to be centuries old it was built only 8 years ago and is a reconstruction of the original damaged structure. Without being overly metaphorical it is an interesting model for what we hope to accomplish with stem cells. Remodeling the old damaged structures with a new one which is exactly what it should have been.

Aaron was able to enjoy the remarkable diversity of cultures and food present in Kiev and this ethnic restaurant was a great experience for us all – even without french fries. I tried a traditional Cossack soup of millet, herbs and mouton (all organic) and on a rather cold day it was exactly what the doctor needed.

Later on Dr Karpenko and I exchanged our thoughts about stem cell therapies and agreed to carefully evaluate the progress of the children being treated so we could more properly describe the effects and therapeutic benefits. This conversation was recorded so in 6-9 months it can be part of the full story on this unique form of potential therapy for autism.

We know that ketotifen helps to stabilize mast cells. So do a variety if natural substances like curcumin. But there seems to be times a medication is required. When it is – ketotifen may be a good choice. Look at what happens when a mast cell is triggered – a huge warehouse of immune chemistry if unloaded.

From a mother of a child with autism: “The pollen became quite high here in the South again on Friday, and it really showed in his behavior – terrible upset and aggression at school. I began using the drops twice a day beginning yesterday, and it really made a positive difference for him. Despite a 3300 pollen count today, his behavior has been good. Ketotifen is the first antihistamine to which my son has not developed an adverse reaction and which also seems to be effective for him — a double win!”

I had recommended she use the OTC Ketotifen eye drops in his nose. This is not always easy in allergy but if you can pull it off it is frequently a WOW – just like this mom tells us.

That complicated graphic explains why – at least in part.

This interesting article from the cardiovascular research arena, shows how remarkably ketotifen protects the heart by suppressing the release of TNF-alpha.

That is exactly the effect we may need in the brain of children with ASD, grandparents with Alzheimer’s and anyone during a heart attack. Recognizing when TNF alpha is not defending, but instead harming us – will be a critical part of progressive medical care.

TNF alpha is critical to most chronic illnesses. Regulating its overexpression is critical – but we are designed to have some TNF alpha all the time, and a whole lot when we need it. So we will need to find ways to determine its proper balance. I think we have that available to us in our proper use of biomarkers of inflammation.

In this graphic the researchers bring our attention to the important subject of sensitizing cells to the TNF effect. I believe this is at the heart of the downward spiral of chronic illnesses.

This link is to an important presentation by the researcher working on the Enbrel® protocol for and therapy for Alzheimer’s. TBI and Stroke. It may be equally important in autism. Please go to the link and click on the video and then listen to his talk. It is important to what I will be talking about in the next series of blogs http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2100099/

And this literature points to the very complex regulatory role of NF- kappa B. It is influenced by TNF and also regulates TNF.

“TNF-α is one of the most prominent pro-inflammatory cytokines significantly increased in AD and it plays a central role in initiating and regulating the cytokine cascade during inflammatory responses. For example, TNF-α increases the expression of adhesionmolecules on the vascular endothelium, which allows leukocytes and immune cells to infiltrate areas of tissue damage and infection.” (I. Granic et al. / NF-κB in Alzheimer’s Disease and Diabetes).

IMMUNE REGULATION OF VASCULAR DISEASE

This quote from Blood Journal illustrates the complexity of the immune regulation of vascular disease. “Atherosclerosis is an inflammatory disease of the arterial wall that carries an important socioeconomic burden. The severe clinical manifestations of atherosclerosis (myocardial infarction, stroke) are mainly due to the abrupt obstruction of the vessel lumen by a thrombus formed on the contact of a ruptured or eroded atherosclerotic plaque. The available data strongly suggest that immunoinflammatory–related mechanisms are the major determinants of plaque complications. Therefore, most of the important advances in the comprehension of the mechanisms of atherosclerosis have come from studies aimed at elucidating the critical components involved in the modulation of the immunoinflammatory balance within the plaque. However, despite the increasing knowledge regarding the role of inflammation in atherogenesis, the precise intracellular transduction pathways involved in this process remain largely unexplored.” (http://bloodjournal.hematologylibrary.org/content/103/3/754.2.full)

Over the next weeks I will be pulling the facts together so you can make better health decisions about all these chronic illnesses including Cancer and HIV and most neurological problems.

The answer is likely. Although the specifics will no doubt be different, if there is a subset of persistent CNS viral infection related autism (as suggested by Persico and others), then the mechanism of impairment may be similar.

The net effect is still that TNF alpha is elevated and with that both direct and indirect harm to neurons will take place. Keeping a lid on TNF and ultimately removing the virus is the target we need to try to shoot for in ASD in the viral-mediated subset.

But can we identify the subset of children affected this way? I think that we can – without performing brain biopsies of course.

I’ve had the pleasure to publish with Dr James onm some very important findings regarding the loss of protection from both toxins and oxidative stress in fairly large cohort of children with autism. The findings, apart from the genetics data more typical of autism, would likely be the same for ALL neurological chronic illnesses including schizophrenia, Parkinsonism, Alzheimer’s and other conditions. ALL of these have been associated with low glutathione levels in the brain. I will explain why this is so important.

Recall Dr Chez’ very important data and observations that even after intervention with anti-inflammatory medications (IVIG, Steroids etc) children with ASD had elevated spinal fluid TNF-alpha (the master inflammatory regulatory messenger of the immune system). He compared CSF TNF-alpha to blood. It should always be less than 1.0(CSF/Blood) and as you can see it never was.

Study this and tonight I will finish the discussion. Right now I have to catch a plane to lecture in South Carolina.

This comment came on one of my think tank blogs from researcher and professor Dick Deth:

“Viruses such as XMRV are suppressed by methylation, and the enzyme methionine synthase is a master controller of methylation. We observed very powerful and rapid inhibition of methionine synthase (MS) transcription by TNF-alpha (>90% decrease of MS mRNA). An examination of the promoter region of methionine synthase revealed a consensus site for NF-kappa-B binding which overlaps the normally promotional AP-1 site. Thus we can hypothesize that TNF-alpha decreases methylation activity via NF-kappa-B.This decrease will augment viral persistence and replication. Notably, MS is very sensitive to oxidative stress, implying that oxidative stress, initiated by any number of provocations, would increase susceptibility to viral infection. Persistent viral infection could in turn prolong/delay recovery from oxidative stress, leading to a persistent oxidative stress and persistent v (a self-reinforcing relationship). In other words we normally recover from an oxidative stress-producing event, but the presence of a viral infection can turn this into a chronic condition…”

This is exactly what we are observing in numerous conditions including XMRV, Autism and ME/CFS. The good news is these conditions can be treated.